Meticulous and consistent use of hand hygiene before and after patient care remains the cornerstone of infection prevention in all health care settings. However, clean hands are not sufficient to prevent all healthcare-associated infections (HAIs), as 1) hands of healthcare workers easily become contaminated from contact with contaminated environmental surfaces in patient rooms after appropriate hand hygiene has been performed and before direct patient care and 2) direct contact by patients with preexisting contaminated environmental surfaces in their hospital rooms can lead to colonization or infection. Thus, novel strategies are needed to prevent HAIs, particularly those caused by multidrug-resistant (MDR) pathogens that persist in the environment such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), Clostridium difficile, and Acinetobacter. Enhanced environmental disinfection methods may lead to reduced risk of exposure to or acquisition of HAIs and MDR-pathogens and overcome a critical issue facing healthcare today - hospitals rooms are often poorly cleaned and disinfected. Enhanced terminal room disinfection strategies using bleach and/or UV-C emitting devices have been investigated only in experimental conditions; the efficacy, effectiveness, and feasibility of enhanced terminal room disinfection to prevent HAIs are unknown. Thus, the scientific evidence for such interventions currently is insufficient for their inclusion in evidence-based guidelines. Our study has three separate but interrelated phases. The first phase is designed to validate and expand upon prior early Phase T1 research on the efficacy and feasibility of using UV-C light emitting devices to reduce the bioburden in patient rooms. Data from this phase will inform study design of phase 2. The second phase will investigate the hypothesis that enhanced terminal room disinfection protocols (using chlorine-based cleaning agents with or without UV-C light-emitting devices) will decrease the overall risk of HAIs in the hospital and, more specifically, in subsequent patients who are cared for in the same room. This prospective investigation will employ a crossover design utilizing four room cleaning/disinfection protocols in 9 hospitals, including 2 tertiary care, 1 VA, and 6 community hospitals. Phase T2 data from this study will be useful in assessing the clinical efficacy and feasibility of individual disinfection strategies. The third phase will utilize microbiologic and molecular techniques to critically and prospectively examine the impact of the environmental bioburden on the risk of colonization and infection of hospitalized patients. Data collected in this phase may provide important information about the mechanisms and relative frequency of how and when environmental sources of bacteria lead to colonization and infection in hospitalized patients. These data may in turn stimulate or justify the future development of novel preventive interventions. Thus, the goals of our proposed research are to 1) determine the appropriate population that would benefit from enhanced terminal room disinfection with UV-C light; 2) determine the efficacy and feasibility of enhanced terminal room disinfection strategies to prevent HAIs; and 3) determine the true impact of environmental contamination on acquisition of MDR-pathogens among hospitalized patients.